AZU1

protein-coding

azurocidin 1, the group of Granule associated serine proteases of immune defence

Gene summary

Azurophil granules, specialized lysosomes of the neutrophil, contain at least 10 proteins implicated in the killing of microorganisms. This gene encodes a preproprotein that is proteolytically processed to generate a mature azurophil granule antibiotic protein, with monocyte chemotactic and antimicrobial activity. It is also an important multifunctional inflammatory mediator. This encoded protein is a member of the serine protease gene family but it is not a serine proteinase, because the active site serine and histidine residues are replaced. The genes encoding this protein, neutrophil elastase 2, and proteinase 3 are in a cluster located at chromosome 19pter. All 3 genes are expressed coordinately and their protein products are packaged together into azurophil granules during neutrophil differentiation. [provided by RefSeq, Nov 2015]

MANE transcript

NM_001700.5

Inheritance

—

ClinVar variants

U:63B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.9

Max pathogenic AF

—

Genomic locus

chr19:825,097-832,018

External References & Databases

Ensembl (ENSG00000172232)

Transcript & Mutation Effects

hg38 • Region Span ~6.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AZU1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 63

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001700.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			63 clinvar			63
nonsense						0
start loss						0
frameshift					1 clinvar	1
splice donor/acceptor (+/-2bp)						0
Total	0	0	63	0	1	64

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001700.5	RefSeq	NP_001691.1	5	MANE Select
ENST00000233997.4	Ensembl	ENSP00000233997.1	5	MANE Select
ENST00000592205.5	Ensembl	ENSP00000481172.1	3	Standard
ENST00001092586.1	Ensembl	ENSP00000762392.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neutrophil degranulation
Innate Immune System
Immune System

Biological Process

microglial cell activation
proteolysis
inflammatory response
protein kinase C-activating G protein-coupled receptor signaling pathway
glial cell migration

Molecular Function

serine-type endopeptidase activity
protein binding
heparin binding
peptidase activity
toxic substance binding

Cellular Component

extracellular region
extracellular space
extrinsic component of membrane
azurophil granule membrane
azurophil granule lumen

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000233997
Coding exons: 5
Length: 6921
Individuals with no LoFs: 125571
Homozygous LoFs: 0
Heterozygous LoFs: 124
Defined: 125695
p: 0.000493

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.132	175	180	0.972	0.0000127	1601
Missense (PolyPhen)		65	68.568	0.94797		637
Synonymous	-0.474	86	80.6	1.07	0.00000606	551
Loss of Function	0.246	7	7.74	0.905	3.32e-7	81

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00032	0.00031	rare
Latino/Admixed American	0.00058	0.00055	rare
Ashkenazi Jewish	0.0016	0.0016	notable
East Asian	0.000055	0.000054	rare
Finnish	0.00029	0.00023	rare
European (Non-Finnish)	0.00055	0.00053	rare
South Asian	0.00050	0.00049	rare
Other	0.00050	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: This is a neutrophil granule-derived antibacterial and monocyte- and fibroblast-specific chemotactic glycoprotein. Binds heparin. The cytotoxic action is limited to many species of Gram- negative bacteria; this specificity may be explained by a strong affinity of the very basic N-terminal half for the negatively charged lipopolysaccharides that are unique to the Gram-negative bacterial outer envelope. It may play a role in mediating recruitment of monocytes in the second wave of inflammation. Has antibacterial activity against the Gram-negative bacterium P.aeruginosa, this activity is inhibited by LPS from P.aeruginosa. Acting alone, it does not have antimicrobial activity against the Gram-negative bacteria A.actinomycetemcomitans ATCC 29532, A.actinomycetemcomitans NCTC 9709, A.actinomycetemcomitans FDC-Y4, H.aphrophilus ATCC 13252, E.corrodens ATCC 23834, C.sputigena ATCC 33123, Capnocytophaga sp ATCC 33124, Capnocytophaga sp ATCC 27872 or E.coli ML-35. Has antibacterial activity against C.sputigena ATCC 33123 when acting synergistically with either elastase or cathepsin G. {ECO:0000269|PubMed:1399008, ECO:0000269|PubMed:1937776, ECO:0000269|PubMed:2312733}.;

Recessive Scores

pRec: 0.400

Intolerance Scores

LoFtool: 0.258
RVIS EVS: 0.4
RVIS percentile EVS: 76.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.145

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium